Chewable product including active ingredient

ABSTRACT

Products and methods of delivering medicaments are provided. The product includes a chewing gum center including a compressible powder that is compressed around the center. The powder includes a medicament that may or may not be encapsulated.

BACKGROUND OF THE INVENTION

[0001] The present invention generally relates to the delivery ofmedicaments and agents. More specifically, the present invention relatesto the delivery of medicaments and agents using products includingchewing gum.

[0002] It is of course known to provide agents to individuals for avariety of purposes. These agents can be used to treat diseases and assuch are typically referred to as drugs or medicaments. Likewise, thedrugs or medicaments can be used for prophylactic purposes. Still, it isknown to provide agents to an individual for a variety of nonmedicalpurposes including enhancing performance or maintaining or initiatingalertness.

[0003] There are a great variety of such agents. These agents run thegamut from stimulants such as caffeine to drugs such as analgesics,tranquilizers, cardiovascular products, insulin, etc. Some such agentsare taken on an as needed basis while other agents must be taken atregular intervals by the individual.

[0004] Typically, drugs (medicaments) are administered parenterally orenterally. Of course, parenteral administration is the administration ofthe drug intravenously directly into the blood stream. Enteral refers tothe administration of the drug into the gastrointestinal tract. Ineither case, the goal of the drug administration is to move the drugfrom the site of administration towards the systemic circulation.

[0005] Except when given intravenously, a drug must traverse severalsemipermeable cell membranes before reaching general circulation. Thesemembranes act as a biological barrier that inhibits the passage of drugmolecules. There are believed to be four processes by which drugs moveacross a biological barrier: passive diffusion; facilitated diffusion;active transport; and pinocytosis.

[0006] Passive diffusion is the transport across the cell membranewherein the driving force for the movement is the concentration gradientof the solute. In orally administered drugs, this absorption occurs inthe small intestines. Facilitated diffusion is believed to be based on acarrier component that combines reversibly with the substrate moleculeat the cell membrane exterior. The carrier substrate complex diffusesrapidly across the membrane with release of the substrate at theinterior surface. Active transport requires an energy expenditure by thecell and appears to be limited to agents with structural similarities tonormal body constituents. These agents are usually absorbed fromspecific sites in the small intestines. Pinocytosis refers to theengulfing of particulars or fluid by a cell. It is believed to play aminor role in drug transport. Merck Manual, 16th Edition, pp. 2598-2599.

[0007] In determining the efficacy of a drug and the effectiveness ofthe use of a drug to treat a disease, drug absorption is a criticalconcern. Drug absorption refers to the process of drug movement from thesite of administration toward the systemic circulation.

[0008] Oral administration of drugs is by far the most common method.When administered orally, drug absorption usually occurs due to thetransport of cells across the membranes of the epithelial cells withinthe gastrointestinal tract. Absorption after oral administration isconfounded by numerous factors. These factors include differences downthe alimentary canal in: the luminal pH; surface area per luminalvolume; perfusion of tissue, bile, and mucus flow; and the epithelialmembranes. See Merck Manual page 2599.

[0009] A further issue effecting the absorption of orally administereddrugs is the form of the drug. Most orally administered drugs are in theform of tablets or capsules. This is primarily for convenience, economy,stability, and patient acceptance. Accordingly, these capsules ortablets must be disintegrated or dissolved in the stomach beforeabsorption can occur. There are a variety of factors capable of varyingor retarding disintegration of solid dosage forms. Further, there are avariety of factors that effect the dissolution rate and thereforedetermine the availability of the drug for absorption. See Merck Manualat page 2600.

[0010] Parenteral administration allows for the direct placement of thedrug into the blood stream. This usually ensures complete delivery ofthe dose to the general circulation. However, administration by a routethat requires drug transfer through one or more biologic membranes toreach the blood stream precludes a guarantee that all of the drug willeventually be absorbed. Even with parental administration, becausecapillaries tend to be highly porous, the perfusion (blood flow/gram oftissue) is a major factor in the rate of absorption. Thus, the injectionsite can markedly influence a drugs' absorption rate; e.g., theabsorption rate of diazepam injected IM into a site with poor blood flowcan be much slower than following an oral dose. See Merck Manual at page2601.

[0011] Not only is drug absorption an issue in drug delivery but, thebioavailability of the drug is also critical. Bioavailability is definedas the rate at which and the extent to which the active moiety (drug ormetabolite) enters the general circulation, thereby gaining access tothe site of action. Bioavailability depends upon a number of factors,including how a drug product is designed and manufactured, itsphysicochemical properties, and factors that relate to the physiologyand pathology of the patient. See Merck Manual at page 2602.

[0012] When a drug rapidly dissolves from a drug product and readilypasses across membranes, absorption from most site administration tendsto be complete. This is not always the case for drugs given orally.Before reaching the vena cava, the drug must move down the alimentarycanal and pass through the gut wall and liver, which are common sites ofdrug metabolism. Thus, the drug may be metabolized before it can bemeasured in the general circulation. This cause of a decrease in druginput is called the first pass effect. A large number of drugs show lowbioavailability owing to an extensive first pass metabolism. The twoother most frequent causes of low bioavailability are insufficient timein the GI tract and the presence of competing reactions. See MerckManual at page 2602.

[0013] Bioavailability considerations are most often encountered fororally administered drugs. Differences in bioavailability can haveprofound clinical significance.

[0014] Although parenteral administration does provide a method foreliminating a number of the variables that are present with oraladministration, parenteral administration is not a preferable route.Typically, parenteral administration requires the use of medicalpersonnel and is just not warranted nor practical for the administrationof most agents and drugs, e.g., analgesics. Even when requiredparenteral administration is not preferred due to patient concernsincluding comfort, infection, etc., as well as the equipment and costsinvolved. However, despite best efforts certain therapies requireparenterally injected drugs. For example, research for decades hasfocused on an attempt to deliver insulin to an individual through anon-parental means. Despite such efforts today insulin is still onlyadministered intravenously.

[0015] There is therefore a need for an improved method of deliveringdrugs and agents to an individual.

SUMMARY OF THE INVENTION

[0016] The present invention provides improved products and methods fordelivering a medicament or agent to an individual. Improved formulationsincluding medicaments or agents are also provided by the presentinvention.

[0017] To this end, the present invention provides a chewing gum productincluding a medicament comprising a chewing gum center and acompressible composition including a medicament, that may beencapsulated, that is compressed around the chewing gum center.

[0018] In an embodiment, the product has a disk shape.

[0019] In an embodiment, the product has a pellet shape.

[0020] In an embodiment, the product has a spherical shape.

[0021] In an embodiment, the product has a cube shape.

[0022] In an embodiment, the encapsulated medicament is encapsulatedwith a composition selected from the group consisting of: naturalpolymers; synthetic polymers; modified cellulosics; and protein.

[0023] In an embodiment, the chewing gum center has the same shape asthe product.

[0024] In an embodiment, the medicament is selected from the groupconsisting of: analgesics; muscle relaxants; antacids; antihistamines;decongestants; anti-inflammatories; antibiotics; anti-virals;psycotherapeutic agents; hormones; cardiovascular agents; vitamins;minerals; and nutriceuticals.

[0025] In an embodiment, the compressible composition includes a maskingagent.

[0026] In another embodiment of the present invention, a compositionincluding a medicament is provided comprising a chewing gum center and acompressible formulation including a medicament that surrounds theentire chewing gum center.

[0027] In an embodiment, the medicament is encapsulated.

[0028] In an embodiment, the medicament is encapsulated with acomposition selected from the group consisting of: natural polymers;synthetic polymers; modified cellulosics; and protein.

[0029] In an embodiment, the medicament is selected from the groupconsisting of: analgesics; muscle relaxants; antacids; antihistamines;decongestants; anti-inflammatories; antibiotics; anti-virals;psycotherapeutic agents; hormones; cardiovascular agents; vitamins;minerals; and nutriceuticals.

[0030] In a further embodiment of the present invention, anacetominophen containing product is provided comprising a chewing gumcenter and a compressible composition including encapsulatedacetaminophen that is compressed around the chewing gum center.

[0031] In yet another embodiment of the present invention a method ofdelivering a medicament is provided comprising the steps of: providing achewing gum center; compressing around the chewing gum center acomposition including a medicament; and causing an individual in need ofthe medicament to chew the product.

[0032] In an embodiment, the medicament is encapsulated.

[0033] In an embodiment, the medicament is selected from the groupconsisting of: analgesics; muscle relaxants; antacids; antihistamines;decongestants; anti-inflammatories; antibiotics; anti-virals;psycotherapeutic agents; hormones; cardiovascular agents; vitamins;minerals; and nutriceuticals.

[0034] Still further, in an embodiment, the present invention provides amethod for providing a medicament comprising the steps of: providing achewing gum center; and compressing around the chewing gum center acomposition including a medicament.

[0035] Additionally, the present invention provides a method ofproducing a medicament containing product comprising the steps of:producing a chewing gum center; and surrounding the chewing gum centerwith a powder that includes a medicament.

[0036] Accordingly, an advantage of the present invention is to providenew methods for delivering medicaments to an individual.

[0037] Furthermore, an advantage of the present invention is to provideimproved products containing a medicament.

[0038] Still further, an advantage of the present invention is toprovide a method of delivering medicaments to an individual thatprovides for increase absorption and bioavailability as compared tomedicaments that are designed to be absorbed in the GI tract.

[0039] Another advantage of the present invention is to provide a novelmethod of delivering medicaments to an individual that provide relieffrom pain symptoms.

[0040] Further, an advantage of the present invention is to providechewing gum products containing medicaments that have excellent contentuniformity.

[0041] Still, an advantage of the present invention is to provide amethod of delivering medicaments that does not require the individual totake water.

[0042] Moreover, an advantage of the present invention is to provide amethod for administering medicaments to an individual that heretoforewere administered parentally.

[0043] Additionally, an advantage of the present invention is to providea method for administering medicaments that is more palatable thancurrent methods.

[0044] Another advantage of the present invention is to provide animproved method for drug delivery.

[0045] An additional advantage of the present invention is that it canprovide an acetaminophen containing product that can be chewed and ispalatable.

[0046] Further, an advantage of the present invention is that a chewinggum product including medicament is provided that can have a variety ofshapes.

[0047] Additional features and advantages of the present invention willbe described in and apparent from the detailed description of theinvention and the figures.

BRIEF DESCRIPTION OF THE DRAWINGS

[0048]FIG. 1 illustrates generally an embodiment of the product of thepresent invention.

[0049]FIG. 2 illustrates graphically the results of Experiment No. 1that is discussed supra.

DETAILED DESCRIPTION OF THE INVENTION

[0050] The present invention provides improved methods for deliveringmedicaments and other agents to an individual as well as improvedproducts including such medicaments or agents.

[0051] Pursuant to the present invention, a medicament is contained in acompressible formulation that surrounds a gum center. As the chewing gumis chewed, the medicament is released into the saliva. During continualchewing, the medicament in the saliva is then forced through the oralmucosa in the buccal cavity due to the pressure created by the chewing.The oral mucosa has a thin epithelium and a rich vascularity. Thus, theoral mucosa favors drug absorption. In contrast to a typically orallyingested drug, wherein the solution is in contact too briefly forabsorption to be appreciable through the oral mucosa, it is believedthat during chewing, the agent and/or medicament remains in the buccalcavity and is forced through the oral mucosa. Also it has beensurprisingly found that an increase in the absorption of the drug isachieved as well as an increase in the bioavailability of the drug ascompared to typical oral administration. It has been found that themedicament is absorbed much quicker than if it was swallowed as in atypical oral administration. Indeed, the absorption may in certain casesapproach that of a parenteral administration, and the bioavailability ismuch greater than oral administration.

[0052] Referring to FIG. 1, an embodiment of the product 10 of thepresent invention is illustrated. As illustrated, the product 10includes a gum center 12. The gum center 12 can be any chewing gumformulation known in the art. Pursuant to the present invention,surrounding the gum center 12 is a compressed powder 14. The compressedpowder 14 is a compressible formulation that is compressed around thechewing gum center 12, and includes a medicament or other active agent.It should be noted, if desired, the gum center can also includemedicaments.

[0053] By using a compressible formulation including a medicament, avariety of shapes and products can be provided. In the preferredembodiment illustrated in FIG. 1, a disk shaped product 10 is provided.However, any geometry can be created, including cubes, pellets, ovals,and spheres. Further, if desired, indicia can be stamped onto thecompressed powder 14 and thereby the product 10 .

[0054] It should be noted that the gum center 12 can either becompletely encased by the compressed powder 14 or it may be partiallyexposed. Further, the gum center 12 may either have the same shape asthe compressed powder 14 and the product 10 or it can have a differentshape. For example, a spherical gum center can be utilized with an ovalcompressed product.

[0055] Pursuant to the present invention, a compressible formulation,powder, is compressed around the chewing gum center in order to form theproduct. This provides advantages over creating chewing gum productsthat may be coated with a medicament. In this regard, typically chewinggum coatings are created by a pan coating process. The present inventionprovides a number of advantages over the pan coating processes. Pancoating processes typically allow for less than 200 mg/piece of theactive agent. There can also be processing control and dosing issueswith respect to products produced using current pan coating processes.Further, pan coated procedures may create stability and shelf lifeissues with respect to the resultant product.

[0056] By utilizing a compressible powder for creating a tabletedproduct, excellent content uniformity can be provided. For example, inan embodiment, it has been found that a product can be provided thatwill have ±3.1% at 300 mg dosage which is ±10.9 mgs.

[0057] As noted above, the compressible powder includes a medicament.The medicament can be blended with a powder to create the compressedpowder through a variety of methods. The blending may be performed by astandard mixing means, using a Vee Blender, a Ribbon Blender or othermixer. The powder is formulated to provide a compressible matrix, usingbulk fillers, sorbitols, sugars, polyols, starches, sugars modified withstarches and the like. Preferably, this filler can range fromapproximately 10 to about 95% by weight composition of the powder andactive/medicament blend. Preferably the active/medicament may range fromapproximately 0.001 to about 60% by weight of the powder andactive/medicament blend. Other components that can be present in thepowder include flavors, colors, sweeteners and high potency sweeteners.Other excipients can also be used in the powder that are useful inmodifying mouthfeel and organoleptic properties of the product.Excipients may also be used to modify dissolution and disintegrationproperties and binding of the product. Preferably the weight of thepowder and active/medicament blend may range from approximately 10 toabout 90% weight of the total product.

[0058] As noted above, if desired, the medicament can be encapsulated orit can be free. In order to produce the encapsulated medicament, avariety of technologies can be utilized. For example, film coatingtechnologies can be used to provide effective taste masking of apharmaceutical agent. A number of materials can be utilized toencapsulate the medicament including, natural polymers, syntheticpolymers, modified cellulose, waxes, fats, oils, and proteins. Inaddition, a diverse range of modifiers can be used, including, but notlimited to, plasticizers, pore formers, disintegrants, waxes, lipids,fats, fatty acids, polylactides, solubilizers, and absorption enhancers.

[0059] Several encapsulating techniques can be used to encapsulate themedicament. These include fluid-bed coating and its variations,low-shear wet granulations, high-shear wet granulations, and spray dryprocesses. The encapsulations provide for coated solid particles andmatrix dispersions. This enhances bioavailability, taste masking, andtailored release profiles. It has been found that high-sheargranulations of active powder with modifying agents provide for tastemasking, absorption enhancement, dissolution aides, and mouth feelmodifiers. The tailored release profile focuses on the immediate releaseof a pharmaceutical/active, a standard delivery profile of pill forms ofmedicaments/actives and delayed or sustained release of a pharmaceuticalactive as given by entreric coating processes.

[0060] The compressed powder can include masking agents. In this regard,high-intensity sweeteners and appropriate flavors can be used to maskany off notes that are present due to the medicament or agent. It hasbeen found that with respect to certain medicaments or agents that mayhave an astringent or bitter taste that by adding a masking agent to theformulation, that a much more palatable formulation, including themedicament, can be provided.

[0061] The masking agents, in an embodiment, are selected from the groupconsisting of sucralose; zinc gluconate; ethyl maltol; glycine;acesulfame-k; aspartame; saccharin; fructose; xylitol; maltitol; coolingagents; isomalt; salt; spray dried licorice root; glycyrrhizin;dextrose; sodium gluconate; sucrose; glucono delta-lactone; ethylvanillin; and vanillin.

[0062] In an embodiment of the invention, sufficient masking agent willbe used in the compressed powder to improve and provide acceptableorganoleptic properties to the chewing gum product. As used herein toprovide “acceptable organoleptic properties” means that the product willhave a sufficiently pleasant, or at least non-offensive taste, to allowthe consumer to chew the chewing gum for at least two minutes. Whether amasking agent is necessary and/or the amount of masking agent will varydepending on medicament. Of course, if desired, more than one maskingagent can be used, e.g., zinc gluconate and a sweetener or flavor. In anembodiment, the masking agent may comprise approximately 10% to about90% by weight of the powder formulation.

[0063] In a preferred embodiment, the compressed powder includes ahigh-intensity sweetener such as aspartame, sucralose, and acesulfame-k.In an embodiment, the high-intensity sweetener comprises approximately0.5% to about 5% by weight of the coating.

[0064] The core, center of the product is chewing gum. It has been foundthat this component of the present invention reduces any aftertaste thatmay be present from the medicament. The gum also speeds delivery of thedrug by increasing production of saliva. The increase in saliva assistsin swallowing the medicament without drinking water. Further anincreased absorption is achieved through oral mucosa by creating fluidpressure.

[0065] Standard gum formulas known in the art can be used for thechewing gum core center of the product. The chewing gum will beformulated in size, mass and texture to minimize chew-in activity ofmedicament into the cud. This can be accomplished by increasing theamount of base and filler in the chewing gum. The amount of gum will beenough to provide a reasonable cud size, e.g., in a range of 0.1 gramsto 3 grams.

[0066] The compression of the powder and medicament blend around thechewing gum center can be performed by modifying existing tabletingequipment presently used in the pharmaceutical industry. For example, amodification can be made to equipment as the Single Layer or MultilayerRotary Tablet Press, to include placement of a core, prior to finalcompression. The powder blend will then surround the gum core center andis mechanically compressed to form the final product.

[0067] It has also been surprisingly found that by placing a medicamentin an powder that is compressed around a gum center less medicament oragent can be placed in the product than is typically orally administeredto an individual to achieve an effect and the same bioequivalence can beachieved. In fact, it has been surprisingly found that in certaininstances, for at least certain drugs and agents, the administration ofthe medicament or agent using chewing gum through the buccal cavity canprovide an increase effect even as compared to parenteraladministration.

[0068] It is envisioned, that a variety of different medicaments andagents can be placed in the compressed powder. Generally, suchmedicaments include, inter alia, analgesics, antibiotics, antivirals,antihistamines, anti-inflammatories, cancer chemotherapies,antimycotics, oral contraceptives, diuretics, antitussives, anesthetics,nutraceuticals, bioengineered pharmaceuticals, oral vaccines,probiotics, decongestants, antacids, muscle relaxants, psychotherapeuticagents, hormones, insulin, vitamins, and minerals and cardiovascularagents. For example, such agents include, inter alia, stimulants such ascaffeine. It is envisioned, that depending on the medicament, theresultant chewing gum can be used to treat, inter alia: coughs; colds;motion sickness; allergies; fevers; pain; inflammation; sore throats;cold sores; sinus problems; diarrhea; diabetics; depression; anxiety;and other maladies and symptoms. Specific agents/medicaments include, byway of example and not limitation: caffeine; aspirin; acetaminophen;ibuprofen; hydroxycitric acid; antacids; chromium picolinate;phosphatidylserine; nicotine (for smoking cessation); insulin; Echinaceapurpurea; zinc; vitamin C; ginseng; kola nut; kaua kaua; and chamomile.

[0069] In an embodiment, the medicaments are contained in the compressedpowder coating of the chewing gum formulation at levels of approximately50 micrograms to 500 milligrams. The specific levels will depend on theactive ingredient. The level of medicament or agent in the compressedpowder of the chewing gum formulation is selected so as to create, whenthe product is chewed, a sufficiently high concentration of themedicament or agent in the saliva.

[0070] In an embodiment of the present invention, the product includesencapsulated acetaminophen. Preferably the product includes at least 250mg of acetaminophen and in an embodiment 500 mg. It has been found thatthe acetaminophen is quickly released from the product into the salivaof the individual chewing the product.

[0071] Pursuant to the present invention, depending on the medicament,the dosing regiment will change. For example, if the medicament is ananalgesic, the chewing gum would be taken on an as needed basis. Ofcourse, similar to the oral administration of an analgesic, there wouldbe restrictions on the number of pieces of chewing gum, chewed, forexample, not more often than one stick every four hours and not moreoften than four to five times a day.

[0072] The powder including medicament can surround a variety ofdifferent gum center compositions. Referring now to the chewing gumcenter, pursuant to the present invention, the gum center may be basedon a variety of different chewing gums that are known. For example, thegum center can be low or high moisture, sugar or sugarless, waxcontaining or wax free, low calorie (via high base or low caloriebulking agents), and/or may contain dental agents.

[0073] Chewing gum generally consists of a water insoluble gum base, awater soluble portion, and flavor. The water soluble portion dissipateswith a portion of the flavor of the gum over a period of time duringchewing. The gum base portion is retained in the mouth throughout thechew.

[0074] The insoluble gum base generally comprises elastomers, resins,fats and oils, softeners and inorganic fillers. The gum base may or maynot include wax. Typically, gum base comprises approximately 20 to about40% of the gum product. However, because in the present invention such ahigh level of coating is used, the gum center is unusually small;otherwise the entire coating chewing gum piece would be too large forconsumption. If atypical amount of gum base was used in the small gumcenter, it would result in an inadequate cud to masticate. Consequently,in the present invention, the base level is higher than normal. Theinsoluble gum base can constitute approximately 30% to about 90% byweight of the chewing gum, in an embodiment, the gum base comprises atleast 50% of the chewing gum.

[0075] In an embodiment, the chewing gum base of the present inventioncontains about 20% to about 60% by weight synthetic elastomer, about 0%to about 30% by weight natural elastomer, about 5% to about 55% byweight elastomer plasticizer, about 4% to about 35% by weight filler,about 5% to about 35% by weight softener, and optional minor amounts(about 1% or less by weight) of miscellaneous ingredients such ascolorants, antioxidants, etc.

[0076] Synthetic elastomers may include, but are not limited to,polyisobutylene with GPC weight average molecular weight of about 10,000to about 95,000, isobutylene-isoprene copolymer (butyl elastomer),styrene-butadiene, copolymers having styrene-butadiene ratios of about1:3 to about 3:1, polyvinyl acetate having GPC weight average molecularweight of about 2,000 to about 90,000, polyisoprene, polyethylene, vinylacetate—vinyl laurate copolymer having vinyl laurate content of about 5%to about 50% by weight of the copolymer, and combinations thereof.

[0077] Preferred ranges for polyisobutylene are 50,000 to 80,000 GPCweight average molecular weight and for styrene-butadiene are 1:1 to 1:3bound styrene-butadiene, for polyvinyl acetate are 10,000 to 65,000 GBCweight average molecular weight with the higher molecular weightpolyvinyl acetates typically used in bubble gum base, and for vinylacetate-vinyl laurate, vinyl laurate content of 10-45%.

[0078] Natural elastomers may include natural rubber such as smoked orliquid latex and guayule as well as natural gums such as jelutong, lechicaspi, perillo, sorva, massaranduba balata, massaranduba chocolate,nispero, rosindinha, chicle, gutta hang kang, and combinations thereof.The preferred synthetic elastomer and natural elastomer concentrationsvary depending on whether the chewing gum in which the base is used isadhesive or conventional, bubble gum or regular gum, as discussed below.Preferred natural elastomers include jelutong, chicle, sorva andmassaranduba balata.

[0079] Elastomer plasticizers may include, but are not limited to,natural rosin esters such as glycerol esters or partially hydrogenatedrosin, glycerol esters of polymerized rosin, glycerol esters ofpartially dimerized rosin, glycerol esters of rosin, pentaerythritolesters of partially hydrogenated rosin, methyl and partiallyhydrogenated methyl esters of rosin, pentaerythritol esters of rosin;synthetics such as terpene resins derived from alpha-pinene,beta-pinene, and/or d-limonene; and any suitable combinations of theforegoing. The preferred elastomer plasticizers will also vary dependingon the specific application, and on the type of elastomer which is used.

[0080] Fillers/texturizers may include magnesium and calcium carbonate,ground limestone, silicate types such as magnesium and aluminumsilicate, clay, alumina, talc, titanium oxide, mono-, di- andtri-calcium phosphate, cellulose polymers, such as wood, andcombinations thereof.

[0081] Softeners/emulsifiers may include tallow, hydrogenated tallow,hydrogenated and partially hydrogenated vegetable oils, cocoa butter,glycerol monostearate, glycerol triacetate, lecithin, mono-, di- andtriglycerides, acetylated monoglycerides, fatty acids (e.g. stearic,palmitic, oleic and linoleic acids); and combinations thereof.

[0082] Colorants and whiteners may include FD&C-type dyes and lakes,fruit and vegetable extracts, titanium dioxide, and combinationsthereof.

[0083] The base may or may not include wax. An example of a wax-free gumbase is disclosed in U.S. Pat. No. 5,286,500, the disclosure of which isincorporated herein by reference.

[0084] In addition to a water insoluble gum base portion, a typicalchewing gum composition includes a water soluble bulk portion and one ormore flavoring agents. The water soluble portion can include bulksweeteners, high-intensity sweeteners, flavoring agents, softeners,emulsifiers, colors, acidulants, fillers, antioxidants, and othercomponents that provide desired attributes.

[0085] Softeners are added to the chewing gum in order to optimize thechewability and mouth feel of the gum. The softeners, which are alsoknown as plasticizers and plasticizing agents, generally constitutebetween approximately 0.5% to about 15% by weight of the chewing gum.The softeners may include glycerin, lecithin, and combinations thereof.Aqueous sweetener solutions such as those containing sorbitol,hydrogenated starch hydrolysates, corn syrup and combinations thereof,may also be used as softeners and binding agents in chewing gum.

[0086] Bulk sweeteners include both sugar and sugarless components. Bulksweeteners typically constitute about 5% to about 95% by weight of thechewing gum, more typically, about 20% to about 80% by weight, and morecommonly, about 30% to about 60% by weight of the gum. Sugar sweetenersgenerally include saccharide-containing components commonly known in thechewing gum art, including but not limited to, sucrose, dextrose,maltose, dextrin, dried invert sugar, fructose, levulose, glactose, cornsyrup solids, and the like, alone or in combination. Sugarlesssweeteners include, but are not limited to, sugar alcohols such assorbitol, mannitol, xylitol, hydrogenated starch hydrolysates, maltitol,and the like, alone or in combination.

[0087] High-intensity artificial sweeteners can also be used, alone orin combination, with the above. Preferred sweeteners include, but arenot limited to, sucralose, aspartame, salts of acesulfame, altitame,saccharin and its salts, cyclamic acid and its salts, glycerrhizinate,dihydrochalcones, thaumatin, monellin, and the like, alone or incombination. In order to provide longer lasting sweetness and flavorperception, it may be desirable to encapsulate or otherwise control therelease of at least a portion of the artificial sweetener. Suchtechniques as wet granulation, wax granulation, spray drying, spraychilling, fluid bed coating, coacervation, and fiber extension may beused to achieve the desired release characteristics.

[0088] Combinations of sugar and/or sugarless sweeteners may be used inchewing gum. Additionally, the softener may also provide additionalsweetness such as with aqueous sugar or alditol solutions.

[0089] If a low calorie gum is desired, a low caloric bulking agent canbe used. Examples of low caloric bulking agents include: polydextrose;Raftilose, Raftilin; Fructooligosaccharides (NutraFlora); Palatinoseoligosaccharide; Guar Gum Hydrolysate (Sun Fiber); or indigestibledextrin (Fibersol). However, other low calorie bulking agents can beused.

[0090] A variety of flavoring agents can also be used, if desired. Theflavor can be used in amounts of about 0.1 to about 15 weight percent ofthe gum, and preferably, about 0.2% to about 5% by weight. Flavoringagents may include essential oils, synthetic flavors or mixtures thereofincluding, but not limited to, oils derived from plants and fruits suchas citrus oils, fruit essences, peppermint oil, spearmint oil, othermint oils, clove oil, oil of wintergreen, anise and the like. Artificialflavoring agents and components may also be used. Natural and artificialflavoring agents may be combined in any sensorially acceptable fashion.

[0091] The gum center can be prepared using a variety of differentmethods and machinery known in the art. For example, the formulation canbe mixed using a sigma blade mixer. The center formulation may also bemade by continuous processing equipment known in the art. Conventionalsheeting and scoring machinery can be used to form and score the centersor the centers can be made on a forming machine that involves a dropframe and nitrogen cooling allowing spheres, ovals, and other shapes tobe made.

[0092] By way of example, and not limitation, examples of some coatedchewing gum formulations including a medicament or agent are as follows:

EXAMPLES

[0093] Examples of formulations follow.

[0094] Chewing Gum Center Formulation, percentage composition: ExampleExample Example Example Example Ingredient 1 2 3 4 5 Sorbitol 30.7030.70 34.80 32.30 35.50 Base 44.00 46.00 41.00 44.00 38.00 Calcium 10.009.00 10.50 10.00 11.00 Carbonate Maltitol 2.00 3.00 1.50 2.00 2.50Glycerin 1.50 5.00 3.50 4.00 4.50 70% Sorbitol 3.50 2.50 3.50 3.50 2.00Solution Flavor 6.00 2.50 2.50 2.50 3.00 Menthol 0.50 — — 0.50 1.00Granulated — 0.50 — 0.50 — Aspartame Encapsulated 0.10 0.10 — 0.50 0.50Aspartame Acesulfame 1.00 — 1.00 — 1.00 K Encapsulated 0.45 — 1.00 —0.30 Sucralose Citric Acid — 0.50 — — 0.40 Lecithin 0.25 0.20 0.20 0.200.30 Total 100.00 100.00 100.00 100.00 100.00 Percentage

[0095] Chewing gum ingredients may be mixed in a Sigma Blade Mixer or ina continuous extruding mixer. After mixing, the gum mass is passedthrough a series of rollers ultimately ending with a pelletizing rollerwhich scored the gum into pieces of the desired mass. Those weremanually reformed into disk shaped pieces. A preferred method would be asheeting method, which would produce the desired disk shaped centerwithout manual manipulation.

[0096] Powder Coating Formulation, percentage composition: ExampleExample Example Example Example Ingredient 6 7 8 9 10 Sorbitol 70.90 — —63.30 — Dextrose — 68.30 — — 60.00 Fructose — — 65.00 — — Encapsulated15.00 — — 22.60 — Aceta- minophen Powder — 18.00 — — — Aceta- minophenGranular — — 20.00 — — Aceta- minophen Granulated — — — — 25.00 Aceta-minophen Polvinyl — 5.00 — — 6.50 pyrolidone Micro- 6.00 — 5.50 6.00 —crystalline Cellulose Aspartame 3.00 2.40 2.00 2.40 5.00 Sucralose 1.502.00 3.50 1.50 — WS-23 0.10 0.20 0.30 0.10 0.25 Calcium — 1.00 — — 0.75Stearate Magnesium 1.00 — 0.60 1.00 — Stearate Flavor 3.00 3.00 3.003.00 2.20 Color 0.10 0.10 0.10 0.10 0.30 Total 100.00 100.00 100.00100.00 100.00 Percentage

[0097] The powder formulations can then be placed around the chewing gumcenters to make a product. For example, a chewing gum as in Example 4was coated with Example 9, by using a calibrated volumetric scoop tomeasure 0.9 grams of powder and poured into the tablet die on a rotarytablet press. The gum center was manually placed on top of the powderand centered, and the volumetric scoop was used to deliver an additional0.9 gm of coating powder over the gum center. The rotary press wascycled through one full rotation to compress the powder around the gumcenter.

Experiment No. 1

[0098] The aforementioned Example 11 was compared to a pan coatedproduct made in the following manner: Chewing gum ingredients may bemixed in a Sigma Blade Mixer or in a continuous extruding mixer. Aftermixing, the gum mass is passed through a series of rollers ultimatelyending with a pelletizing roller which scored the gum into pieces of thedesired shape and size.

[0099] The gum centers were loaded into a conventional perforated panand coated in a manner typical of standard confections. The pellet bedwas doused with syrup and allowed to tumble for a period of time todistribute the syrup and dried for another fixed period of time. Duringthe intermediate phases of this process, a dry charge consisting ofmaltitol and powdered acetaminophen was sprinkled on the moist bed ofpellets and incorporated into the pellet coating prior to completedrying. This is repeated as necessary to build up the desired drug doseon the outside of the pellets.

[0100] Kinetic analysis was performed on three subjects to determine theamount of acetaminophen, which was chewed into the cud. The comparativeexamples used were Driam pan coated gum with a 195 mg/pellet ofacetaminophen and Driam pan coated gum with 150 mg/pellet ofacetaminophen were compared to the experimental samples of CompressedTablet Chewing Gum with 355 mg/pellet of acetaminophen. The time pointstaken for the pan coated 195 mg/pellet product were at 0, 2, 5, 10 and20 minutes. Time points for the 150 mg/pellet product were at 0, 10, 20,30, and 40 minutes. The time points taken for the Compressed TabletChewing Gum 355 mg/pellet product were 0, 1, 3, 5, 8, 14, and 20minutes.

[0101]FIG. 2 illustrates graphically the results of this analysis.

[0102] It should be understood that various changes and modifications tothe presently preferred embodiments described herein will be apparent tothose skilled in the art. Such changes and modifications can be madewithout departing from the spirit and scope of the present invention andwithout diminishing its intended advantages. It is therefore intendedthat such changes and modifications be covered by the appended claims.

1. A chewing gum product including a medicament comprising: a chewinggum center; and a compressible composition comprising an encapsulatedmedicament that is compressed around the chewing gum center.
 2. Thechewing gum product of claim 1 wherein the product has a disk shape. 3.The chewing gum product of claim 1 wherein the product has a pelletshape.
 4. The chewing gum product of claim 1 wherein the product has aspherical shape.
 5. The chewing gum product of claim 1 wherein theproduct has a cube shape.
 6. The chewing gum product of claim 1 whereinthe encapsulated medicament is encapsulated with a composition selectedfrom the group consisting of: natural polymers; synthetic polymers;modified cellulosics; waxes; fats; oils; and protein.
 7. The chewing gumproduct of claim 1 wherein the chewing gum center has the same shape asthe product.
 8. The chewing gum product of claim 1 wherein themedicament is selected from the group consisting of: analgesics; musclerelaxants; antacids; antihistamines; decongestants; anti-inflammatories;oral vaccines; probiotics; antibiotics; anti-virals; cancerchemotherapies; antimycotics; oral contraceptives; diuretics;antitussives; anesthetics; bioengineered pharmaceuticals;psycotherapeutic agents; hormones; cardiovascular agents; vitamins;insulin; minerals; and nutraceuticals.
 9. The chewing gum product ofclaim 1 wherein the compressible composition includes a masking agent.10. composition including a medicament comprising: a chewing gum center;and a compressible formulation including a medicament that surrounds theentire chewing gum center.
 11. The composition of claim 10 wherein themedicament is encapsulated.
 12. The composition of claim 10 wherein thechewing gum composition has a disk shape.
 13. The composition of claim10 wherein the medicament is encapsulated with a composition selectedfrom the group consisting of: natural polymers; synthetic polymers;modified cellulosics; waxes; fats; oils; and protein.
 14. Thecomposition of claim 10 wherein the medicament is selected from thegroup consisting of: analgesics; muscle relaxants; antacids;antihistamines; decongestants; anti-inflammatories; antibiotics;anti-virals; oral vaccines; probiotics; psycotherapeutic agents;hormones; cardiovascular agents; vitamins; minerals; insulin; andnutraceuticals.
 15. An acetominophen containing product comprising: achewing gum center; and a compressible composition includingencapsulated acetaminophen that is compressed around the chewing gumcenter.
 16. The acetominophen containing product of claim 15 wherein theproduct has a disk shape.
 17. The acetominophen containing product ofclaim 15 wherein the acetominophen is encapsulated with a compositionselected from the group consisting of: natural polymers; syntheticpolymers; modified cellulosics; waxes; fats; oils; and protein.
 18. Theacetominophen containing product of claim 15 wherein the chewing gumcenter has the same shape as the product.
 19. A method of delivering amedicament comprising the steps of: providing a chewing gum center;compressing around the chewing gum center a composition including amedicament to produce a product; and causing an individual in need ofthe medicament to chew the product.
 20. The method of claim 19 whereinthe medicament is encapsulated.
 21. The method of claim 20 wherein themedicament is encapsulated with a composition selected from the groupconsisting of: natural polymers; synthetic polymers; modifiedcellulosics; and protein.
 22. The method of claim 19 wherein the productis chewed a plurality of times per day.
 23. The method of claim 19wherein the medicament is selected from the group consisting of:analgesics; muscle relaxants; antacids; antihistamines; decongestants;anti-inflammatories; antibiotics; anti-virals; oral vaccines;probiotics; cancer chemotherapies; antimycotics; oral contraceptives;diuretics; antitussives; anesthetics; bioengineered pharmaceuticals;insulin; psycotherapeutic agents; hormones; cardiovascular agents;vitamins; minerals; and nutraceuticals.
 24. The method of claim 19wherein the medicament is acetominophen.
 25. A method for providing amedicament comprising the steps of: providing a chewing gum center; andcompressing around the chewing gum center a composition including amedicament.
 26. The method of claim 25 wherein the medicament isencapsulated with a composition selected from the group consisting of:natural polymers; synthetic polymers; modified cellulosics; waxes; fats;oils; and protein.
 27. The method of claim 25 wherein the medicament isselected from the group consisting of: analgesics; muscle relaxants;antacids; antihistamines; decongestants; anti-inflammatories;antibiotics; anti-virals; cancer chemotherapies; antimycotics; oralcontraceptives; diuretics; antitussives; anesthetics; oral vaccines;probiotics; bioengineered pharmaceuticals; insulin; psycotherapeuticagents; hormones; cardiovascular agents; vitamins; minerals; andnutraceuticals.
 28. The method of claims 25 wherein the medicament isacetominophen.
 29. A method of producing a medicament containing productcomprising the steps of: producing a chewing gum center; and surroundingthe chewing gum center with a compressible powder that includes amedicament.
 30. The method of claim 29 wherein the medicament isencapsulated with a composition selected from the group consisting of:natural polymers; synthetic polymers; modified cellulosics; and protein.31. The method of claim 29 wherein the medicament is selected from thegroup consisting of: analgesics; muscle relaxants; antacids;antihistamines; decongestants; anti-inflammatories; antibiotics;anti-virals; cancer chemotherapies; antimycotics; oral contraceptives;diuretics; antitussives; anesthetics; bioengineered pharmaceuticals;psycotherapeutic agents; hormones; cardiovascular agents; oral vaccines;probiotics; insulin; vitamins; minerals; and nutraceuticals.
 32. Themethod of claim 29 including the step of compressing the powder aroundthe chewing gum center.